TY - JOUR
T1 - Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer
T2 - A phase 1b JAVELIN solid tumor study
AU - Dirix, Luc Y.
AU - Takacs, Istvan
AU - Jerusalem, Guy
AU - Nikolinakos, Petros
AU - Arkenau, Hendrik Tobias
AU - Forero-Torres, Andres
AU - Boccia, Ralph
AU - Lippman, Marc E.
AU - Somer, Robert
AU - Smakal, Martin
AU - Emens, Leisha A.
AU - Hrinczenko, Borys
AU - Edenfield, William
AU - Gurtler, Jayne
AU - von Heydebreck, Anja
AU - Grote, Hans Juergen
AU - Chin, Kevin
AU - Hamilton, Erika P.
PY - 2018/10/23
Y1 - 2018/10/23
N2 - Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
AB - Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
KW - Avelumab
KW - Metastatic breast cancer
KW - PD-L1
KW - Second-line
KW - Triple-negative breast cancer
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U2 - 10.1007/s10549-017-4537-5
DO - 10.1007/s10549-017-4537-5
M3 - Article
C2 - 29063313
AN - SCOPUS:85031927832
VL - 167
SP - 671
EP - 686
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 3
ER -